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About me

I am a senior researcher in the group of Professor Lennart Hammarström at the Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine. I am supervising the Immunotherapy group and my research focus on passive immunization using Lactobacillus expressing antibody fragments against mucosal pathogens.

Education

1987-1990  B.Sc. in Microbiology, Department of Biochemistry, Université Laval, Canada
 
1990-1992 M.Sc. in Microbiology, Department of Biochemistry, Université Laval, Canada
 
1992-1997 Ph.D. in Microbiology and Immunology, Faculty of Medecine, Université Laval, Canada

 

Thesis (Msc and PhD):

Harold Marcotte. “Étude de la variabilité dans les interactions hôte-bactéries chez la souris BALB/c ”, Thèse (MSc), Université Laval, 1992. http://worldcat.org/oclc/77357770

Harold Marcotte. “Interactions entre les IgA salivaires et la microflore buccale chez la souris”, Thèse (PhD), Université Laval, 1997.
http://worldcat.org/oclc/77313566

Research description

Passive administration of antibodies represents the therapy of choice for mucosal infections, particularly in children and immunocompromised individuals and during the past two decades, oral administration of polyclonal antibodies against selected enteric pathogens has been employed successfully. However, production and purification of these antibodies is costly and therefore, efforts have been made to develop new methods for production of monoclonal antibodies or antibody fragments employing plant, yeast and bacterial systems.

An attractive idea is to use lactobacilli as vectors for in situ delivery of antibody fragments and other therapeutic molecules at mucosal surfaces. Lactobacilli are Gram-positive bacteria with a long history of safe use in food fermentation and preservation. They are also a significant component of the naturally occuring gastrointestinal and vaginal microbiota. The desired genes can be integrated into the bacterial genome, creating food grade, genetically modified lactobacilli. The modified lactobacilli can be freeze-dried or spray dried and subsequently incorporated in capsules or food products. We have previously shown that genetically modified lactobacilli delivering antibody fragments against S. mutans (Krüger et al. 2002), rotavirus (Pant et al. 2006, Alvarez et al. 2015), and C. difficile (Andersen et al. 2015) are protective in animal models. In addition, lactobacilli can be used to deliver a ranged of therapeutic molecules in the gastrointestinal tract such as cytokines, antimicrobial peptides and glucacon-like peptides.

Our current research projects include:

- Generation of antibody fragments against mucosal pathogens

- Delivery of antibody fragments against mucosal pathogens (norovirus, HIV) by lactobacilli

- Lactobacilli delivering cytokines (IL-10, IL-21, IL-22) and CD40L for treatment of inflammatory diseases and IgA deficiency

- Treatment of bacterial vaginosis using a combination of antibiotics and probiotics

Teaching portfolio

 

I have always been employed to conduct 100% research since I began as a postdoctoral fellow at KI and all teaching performed has been on an invited basis.

I am currently teaching immunology for the Biomedicine Laboratory Science program (Biomedicinska analytikerprogrammet).

I am also currently supervising one visiting PhD student.

Documents

Links

Publications

Our gut microbiota: a long walk to homeostasis
Dicks Lmt, Geldenhuys J, Mikkelsen Ls, Brandsborg E, Marcotte H
Beneficial microbes 2018;9(1):3-20

Characterization and complete genome sequences of L. rhamnosus DSM 14870 and L. gasseri DSM 14869 contained in the EcoVag® probiotic vaginal capsules
Marcotte H, Krogh Andersen K, Lin Y, Zuo F, Zeng Z, Larsson Pg, et al
Microbiological research 2017;205():88-98

Lactobacillus delivery of bioactive interleukin-22
Lin Y, Krogh-andersen K, Hammarström L, Marcotte H
Microbial cell factories 2017;16(1):148-

Fusion of the mouse IgG1 Fc domain to the VHH fragment (ARP1) enhances protection in a mouse model of rotavirus
Günaydın G, Yu S, Gräslund T, Hammarström L, Marcotte H
Scientific reports 2016;6():30171-

Neutralization of Clostridium difficile Toxin B Mediated by Engineered Lactobacilli That Produce Single-Domain Antibodies
Andersen Kk, Strokappe Nm, Hultberg A, Truusalu K, Smidt I, Mikelsaar Rh, et al
Infection and immunity 2016;84(2):395-406

Oral Delivery of Pentameric Glucagon-Like Peptide-1 by Recombinant Lactobacillus in Diabetic Rats
Lin Y, Krogh-andersen K, Pelletier J, Marcotte H, Östenson Cg, Hammarström L
PloS one 2016;11(9):e0162733-

An Exopolysaccharide-Deficient Mutant of Lactobacillus rhamnosus GG Efficiently Displays a Protective Llama Antibody Fragment against Rotavirus on Its Surface
Álvarez B, Krogh-andersen K, Tellgren-roth C, Martínez N, Günaydın G, Lin Y, et al
Applied and environmental microbiology 2015;81(17):5784-93

Vaginal colonisation by probiotic lactobacilli and clinical outcome in women conventionally treated for bacterial vaginosis and yeast infection
Pendharkar S, Brandsborg E, Hammarström L, Marcotte H, Larsson Pg
BMC infectious diseases 2015;15():255-

Co-expression of anti-rotavirus proteins (llama VHH antibody fragments) in Lactobacillus: development and functionality of vectors containing two expression cassettes in tandem
Günaydın G, Alvarez B, Lin Y, Hammarström L, Marcotte H
PloS one 2014;9(4):e96409-

Engineered Lactobacillus rhamnosus GG expressing IgG-binding domains of protein G: Capture of hyperimmune bovine colostrum antibodies and protection against diarrhea in a mouse pup rotavirus infection model
Günaydın G, Zhang R, Hammarström L, Marcotte H
Vaccine 2014;32(4):470-7

Identification and characterisation of vaginal lactobacilli from South African women
Pendharkar S, Magopane T, Larsson Pg, De Bruyn G, Gray Ge, Hammarström L, et al
BMC infectious diseases 2013;13():43-

Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection
Tokuhara D, Alvarez B, Mejima M, Hiroiwa T, Takahashi Y, Kurokawa S, et al
JOURNAL OF CLINICAL INVESTIGATION 2013;123(9):3829-38

Extended antimicrobial treatment of bacterial vaginosis combined with human lactobacilli to find the best treatment and minimize the risk of relapses
Larsson Pg, Brandsborg E, Forsum U, Pendharkar S, Andersen Kk, Nasic S, et al
BMC INFECTIOUS DISEASES 2011;:223-

In situ gastrointestinal protection against anthrax edema toxin by single-chain antibody fragment producing lactobacilli
Andersen Kk, Marcotte H, Alvarez B, Boyaka Pn, Hammarstrom L
BMC BIOTECHNOLOGY 2011;:126-

Integrative Expression System for Delivery of Antibody Fragments by Lactobacilli
Martin Mc, Pant N, Ladero V, Gunaydin G, Andersen Kk, Alvarez B, et al
APPLIED AND ENVIRONMENTAL MICROBIOLOGY 2011;77(6):2174-9

Lactobacilli producing bispecific llama-derived anti-rotavirus proteins in vivo for rotavirus-induced diarrhea
Pant N, Marcotte H, Hermans P, Bezemer S, Frenken L, Johansen K, et al
FUTURE MICROBIOLOGY 2011;6(5):583-93

Safety and persistence of orally administered human Lactobacillus sp strains in healthy adults
Hutt P, Koll P, Stsepetova J, Alvarez B, Mandar R, Krogh-andersen K, et al
BENEFICIAL MICROBES 2011;2(1):79-90

Screening and Evaluation of Human Intestinal Lactobacilli for the Development of Novel Gastrointestinal Probiotics
Koll P, Mandar R, Smidt I, Hutt P, Truusalu K, Mikelsaar Rh, et al
CURRENT MICROBIOLOGY 2010;61(6):560-6

Characterization of oral lactobacilli as potential probiotics for oral health
Koll P, Mandar R, Marcotte H, Leibur E, Mikelsaar M, Hammarstro L
ORAL MICROBIOLOGY AND IMMUNOLOGY 2008;23(2):139-47

Engineered lactobody-producing lactobacilli: a novel form of therapy against rotavirus infection
Marcotte H, Pant N, Hammarstrom L
FUTURE VIROLOGY 2008;3(4):327-341

Effective prophylaxis against rotavirus diarrhea using a combination of Lactobacillus rhamnosus GG and antibodies
Pant N, Marcotte H, Brussow H, Svensson L, Hammarstrom L
BMC MICROBIOLOGY 2007;:86-

Lactobacillli expressing llama VHH fragments neutralise Lactococcus phages
Hultberg A, Tremblay Dm, De Haard H, Verrips T, Moineau S, Hammarstom L, et al
BMC BIOTECHNOLOGY 2007;:58-

Expression of single-chain antibody against RgpA protease of Porphyromonas gingivalis in Lactobacillus
Marcotte H, Koll-klais P, Hultberg A, Zhao Y, Gmur R, Mandar R, et al
JOURNAL OF APPLIED MICROBIOLOGY 2006;100(2):256-63

Lactobacilli expressing variable domain of llama heavy-chain antibody fragments (lactobodies) confer protection against rotavirus-induced diarrhea
Pant N, Hultberg A, Zhao Yf, Svensson L, Pan-hammarstrom Q, Johansen K, et al
JOURNAL OF INFECTIOUS DISEASES 2006;194(11):1580-8

Therapeutic effect of llama derived VHH fragments against Streptococcus mutans on the development of dental caries
Kruger C, Hultberg A, Marcotte H, Hermans P, Bezemer S, Frenken Lgj, et al
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 2006;72(4):732-7

Oral lactobacilli in chronic periodontitis and periodontal health: species composition and antimicrobial activity
Koll-klais P, Mandar R, Leibur E, Marcotte H, Hammarstrom L, Mikelsaar M
ORAL MICROBIOLOGY AND IMMUNOLOGY 2005;20(6):354-61

Passive immunization by lactobacilli expressing single-chain antibodies against Streptococcus mutans
Kruger C, Hultberg A, Van Dollenweerd C, Marcotte H, Hammarstrom L
MOLECULAR BIOTECHNOLOGY 2005;31(3):221-31

Mucosal and cellular immune responses elicited by recombinant Lactococcus lactis strains expressing tetanus toxin fragment C
Robinson K, Chamberlain Lm, Lopez Mc, Rush Cm, Marcotte H, Le Page Rwf, et al
INFECTION AND IMMUNITY 2004;72(5):2753-61

The aggregation-promoting factor of Lactobacillus crispatus M247 and its genetic locus
Marcotte H, Ferrari S, Cesena C, Hammarstrom L, Morelli L, Pozzi G, et al
JOURNAL OF APPLIED MICROBIOLOGY 2004;97(4):749-56

In situ delivery of passive immunity by lactobacilli producing single-chain antibodies
Kruger C, Hu Yz, Pan Q, Marcotte H, Hultberg A, Delwar D, et al
NATURE BIOTECHNOLOGY 2002;20(7):702-6

Immunization with recombinant Streptococcus gordonii expressing tetanus toxin fragment C confers protection from lethal challenge in mice
Medaglini D, Ciabattini A, Spinosa Mr, Maggi T, Marcotte H, Oggioni Mr, et al
VACCINE 2001;19(15-16):1931-9

Immunoglobulin-binding domains of peptostreptococcal protein L enhance vaginal colonization of mice by Streptococcus gordonii
Ricci S, Medaglini D, Marcotte H, Olsen A, Pozzi G, Bjorck L
MICROBIAL PATHOGENESIS 2001;30(4):229-35

Oral microbial ecology and the role of salivary immunoglobulin A
Marcotte H, Lavoie Mc
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS 1998;62(1):71-109

Comparison of the indigenous oral microbiota and immunoglobulin responses of athymic (nu/nu) and euthymic (nu/+) mice
Marcotte H, Lavoie Mc
Oral microbiology and immunology 1997;12(3):141-7

No apparent influence of immunoglobulins on indigenous oral and intestinal microbiota of mice
Marcotte H, Lavoie Mc
INFECTION AND IMMUNITY 1996;64(11):4694-9

Pneumocystis carinii infection in transgenic B cell-deficient mice
Marcotte H, Levesque D, Delanay K, Bourgeault A, Deladurantaye R, Brochu S, et al
JOURNAL OF INFECTIOUS DISEASES 1996;173(4):1034-7

COLONIZATION OF THE ORAL CAVITY OF MICE BY AN UNIDENTIFIED STREPTOCOCCUS
Marcotte H, Rodrigue L, Coulombe C, Goyette N, Lavoie Mc
ORAL MICROBIOLOGY AND IMMUNOLOGY 1995;10(3):168-74

Immunization against the oral indigenous bacteria of the BALB/c mouse
Marcotte H, Rodrigue L, Gamache M, Lavoie Mc
Advances in experimental medicine and biology 1995;371B():1173-6

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